ABSTRACT In this application, we are requesting funds to acquire an XtremeCT II High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) scanner. This is a unique imaging modality enabling in vivo accurate and precise three-dimensional measurements of volumetric bone mineral density (vBMD), bone geometry, trabecular bone microarchitecture, cortical bone microstructure, and biomechanics at the distal radius and distal tibia across the lifespan. Assessment of multiple parameters of bone density and quality with HR-pQCT provides a better understanding of the different factors contributing to bone strength and fracture risk. The University of Colorado Anschutz Medical Campus (CU-AMC) has a collaborative, enthusiastic, interdisciplinary group of investigators experienced in metabolic bone disease research. This group includes experts in imaging, clinical trials, mechanical engineering and image analysis, who would greatly benefit from all the capabilities of the HR-pQCT scanner to strengthen their research and test novel hypotheses that cannot be pursued with other imaging modalities. The device will also allow CU-AMC investigators to develop more collaborations with investigators at CU-AMC affiliates including Children?s Hospital Colorado, CU Denver, CU Colorado Springs and CU Boulder, as well as with investigators across the nation. In particular, HR-pQCT would enable investigators at CU-AMC to: 1) evaluate whether the musculoskeletal adaptations to bone- loading exercise can be significantly augmented in older women with low bone mass or moderate osteoporosis by restoring serum dehydroepiandrosterone sulfate (DHEAS) to young adult levels; 2) expand the investigation of the skeletal effects of changes in follicle stimulating hormone (FSH) vs. estradiol from areal BMD (aBMD) only, to cutting-edge metrics of bone strength and quality; 3) address important gaps on the effects of exercise on bone, and investigate the different skeletal adaptations to weight-bearing endurance vs. resistance exercise; 4) elucidate the influence of progressive exercise and changes in sex hormones (testosterone and its metabolites) and glycoprotein (follistatin) concentrations on female bone microarchitecture and strength; 5) demonstrate the potential of advanced image analyses techniques for multi-parametric spatial assessments of bone in adolescents with obesity; 6) assess the efficacy and safety of abaloparatide for the treatment of osteoporosis in men; and 7) assess the effect of abaloparatide plus standard of care vs. placebo plus standard of care on delayed fracture healing. In addition, HR-pQCT will expand ongoing interdisciplinary bone research at CU-AMC as it pertains to chronic kidney disease, the skeletal effects of HIV/cancer, transgender medicine, bariatric surgery, and diabetes. This device will also help develop the next generation of bone scientists at CU- AMC. Ultimately, the addition of an HR-pQCT system will enable CU-AMC investigators to engage in more collaborations, compete more successfully for musculoskeletal research funding, and remain at the forefront of metabolic bone disease research across the lifespan.